Activation of neurons in the basolateral amygdala (BLA) plays an essential role in the cellular processes that underlie the normal, adaptive, behavioral response to threatening, as well as rewarding, environmental stimuli. Importantly, release of the neurotransmitter dopamine has also been shown to play a central role in the response to threatening or rewarding stimuli. Moreover, several neuropsychiatric disorders such as schizophrenia, which are commonly associated with emotional disturbances, are thought to result, at least in part, from abnormal dopamine transmission. Compelling evidence now suggests that region-specific release of dopamine into the BLA is an absolute requirement for the formation of fearful memories. Hence, dopamine depletion prevents the formation of fear memories, an effect that can be rescued by allowing dopamine release to occur only within the BLA. More specifically, pharmacological agents that selectively modulate the activity of D1 family dopamine receptors (D1R, including D1 and D5) in the BLA can also modulate fear memory formation and consolidation. Significantly, gene knockout mice with a global deletion of D1 receptors show an impairment of fear memory formation. In other brain regions, D1 receptors are believed to activate the protein kinase-A (PKA) cascade. Importantly, inactivation of the PKA pathway impairs fear memory formation. Together, these data suggest that activation of the D1 - PKA cascade in the BLA may play a critical role in the formation of fear memories. Similarly, recent studies have indicated that synchronized neural activity, both within the BLA and between the BLA and target structures such as the medial prefrontal cortex (mPFC), play a major role in memory formation and recall. Dopamine has long been known to play a critical role in synchronizing neural activity. However, no study has systematically examined the molecular, cellular, and network-level mechanisms by which D1 receptor activation may facilitate fear memory formation. The studies outlined in this proposal are designed to address this significant knowledge gap. We have strong preliminary data to support our hypothesis that: D1 receptor activation in BLA principal neurons acts to facilitate synaptic plasticity by a PKA-dependent enhancement of intrinsic membrane oscillations and spike timing precision. The resulting highly synchronized firing of principal neurons in distinct frequency ranges, and subsequent phase locking of synchronized activity between the BLA and mPFC, facilitates fear memory formation. The specific aims of this proposal have been designed to answer three specific questions relating to this hypothesis: SA#1. Does activation of the D1 - PKA cascade facilitate intrinsic oscillatory activity in the BLA? SA#2. Is activation of the D1 - PKA cascade necessary for synaptic plasticity in BLA afferent inputs? SA#3. Can activation of the D1 - PKA cascade facilitate coherent oscillations between the BLA and mPFC during fear learning?